Comparison of hypofractionation and conventional fractionation in postmastectomy radiotherapy after immediate breast reconstruction: A systematic review and meta-analysis of complications.

BACKGROUND: The optimal radiotherapy regimen following mastectomy and immediate breast reconstruction remains under active investigation. In particular, the safety of moderate hypofractionation (HF) compared to conventional fractionation (CF) for postmastectomy radiotherapy (PMRT) has not been clearly established. Given the growing adoption of HF in breast cancer treatment, a thorough synthesis comparing complication outcomes is essential to guide clinical practice. METHODS: A comprehensive search was conducted in Embase, MEDLINE, and Cochrane CENTRAL up to January 10, 2025. Studies comparing HF (2.4-2.7 Gy/fraction) and CF (1.8-2.0 Gy/fraction) in patients undergoing immediate breast reconstruction with PMRT were included. Studies involving partial breast irradiation or accelerated fractionation were excluded. Risk of bias was assessed using RoB 2 and ROBINS-I V2; certainty of evidence was evaluated using GRADE. A random-effects meta-analysis was performed, estimating pooled odds ratios (ORs) with 95 % confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023471267). RESULTS: Eleven studies (n = 3611), including three randomized controlled trials, were included. HF and CF demonstrated similar risks of major complications (OR: 0.83; 95 % CI: 0.51-1.35; p = 0.45; n = 5). No significant differences were observed for infection, wound dehiscence, or hematoma among photon-based studies. HF was associated with a lower risk of capsular contracture (OR: 0.38; 95 % CI: 0.15-0.99; p = 0.05; n = 5). Only one study evaluated quality of life, reporting no difference in physical well-being. CONCLUSIONS: HF offers a safety profile comparable to CF following breast reconstruction and may be preferred due to its reduced treatment burden and a potentially lower risk of capsular contracture.